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Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease.

Abstract：

:The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways1, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin β7+ natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7- mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-12, which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.

journal_name

Nature

journal_title

Nature

authors

He S,Kahles F,Rattik S,Nairz M,McAlpine CS,Anzai A,Selgrade D,Fenn AM,Chan CT,Mindur JE,Valet C,Poller WC,Halle L,Rotllan N,Iwamoto Y,Wojtkiewicz GR,Weissleder R,Libby P,Fernández-Hernando C,Drucker DJ,Nahrendorf

doi

10.1038/s41586-018-0849-9

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

115-119

issue

7742

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-018-0849-9

journal_volume

566

pub_type

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